Glucocorticoid regulation of rat diencephalon angiotensinogen production.
To investigate whether glucocorticoids can stimulate rat brain angiotensinogen production directly, we have studied the effect of dexamethasone on angiotensinogen secretion and angiotensinogen mRNA concentration in primary astroglial cultures from rat diencephalon. Dexamethasone stimulated angiotensinogen secretion by astroglial cells in a dose-related fashion. The half-maximally effective concentration was 11 nM, and the effect was blocked by RU 486, an antagonist of type II glucocorticoid receptors. This was similar to what was observed in rat hepatoma H4IIEC cells, where the half-maximally effective concentration of dexamethasone on angiotensinogen secretion was 10 nM. At maximal concentrations, dexamethasone increased angiotensinogen secretion and angiotensinogen mRNA concentration 2-fold in astroglial cells. In the hepatoma cells, however, the increase in angiotensinogen secretion was 5-fold. The in vivo diencephalon angiotensinogen mRNA concentration was decreased after adrenalectomy. Dexamethasone restored those levels to normal and induced a modest increase when the animals were killed 6 h after drug administration. In contrast, dexamethasone induced a robust increase in liver angiotensinogen mRNA concentration in the same animals. These results indicate that glucocorticoids increase angiotensinogen production through a direct receptor-mediated mechanism in both liver and brain. However, the angiotensinogen gene appears much more responsive to the action of glucocorticoids in liver than in brain.
Deschepper
C F
CF
Department of Physiology, University of California, San Francisco 94143-0444.
Flaxman
M
M
D000315:Adrenalectomy; D000808:Angiotensinogen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004027:Diencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D000808:Angiotensinogen; D015735:Mifepristone; D003907:Dexamethasone